Metrics details Previous studies have reported silicone oil (SO) applied to needles and syringes in the vitreous of patients after intravitreal injections We evaluated four syringes (SR 1-mL insulin Saldanha-Rodrigues; BD 1-mL Tuberculin Slip Tip Henke Sass Wolf) and 10 needles (BD PrecisionGlide 27- and 30-gauge (G); BD Eclipse and JBP Nanoneedle 27- 33- and 34-G; TSK Invisible Needle and 27 and 30-G Steriject Control Hub) The protein-free buffer samples injected into the syringes and needles under study were collected in an Eppendorf tube and taken to Flow imaging microscopy that characterized the concentration and morphology of the microsized particles The coefficients of variation (CV) were the primary outcome The Feltz and Miller test compared the CVs Numerous particles and high CVs were associated with both devices needles and syringes; the comparisons among them did not reach significance The BD Ultrafine 0.3 mL syringe (149.7%) had the highest CV and the SO-free HSW Norm-Ject (66.4%) syringe the lowest and the TSK Invisible needle (149.5%) had the highest and the BD Precision Glide 30G needle (35.9%) needle the lowest which is relevant considering that fewer particles are injected into some eyes compared with others the clinical importance of achieving the most efficient lubrication possible using minimal SO to achieve uniform coating of the materials is imperative While the physicians administering IVIs expect that syringes and needles have a consistent and predictable amount of lubricant high variability in that amount of SO can lead to heterogenous release of particles into the vitreous The current study assessed both the levels of particles released by some of the most popular syringe and needle models used by ophthalmologists worldwide and their variability across samples from the same lot Forty syringes, 10 of each model from a specific manufacturing lot, were assessed. The levels of particles (including those with SO morphology) released from each model are listed in Table 1 Large numbers of particles and a significantly high coefficients of variation (CVs) were seen The CV was highest in the BD Ultrafine 0.3 mL (149.7%) and lowest in the SO-free HSW Norm-Ject (66.4%) syringes The BD Tuberculin and SR syringes had CVs of 111.6% and 118% Coefficients of variation (CV) of the syringe models The Feltz and Miller asymptomatic test was used for CV comparisons—Chi2(3) = 1.47 (p = 0.689) Illustrative examples of particles from the syringes seen in flow imaging microscopy images a Circular particles from the HSW Norm-Ject with circular particles consistent with SO droplets c Particles from the BD-Tuberculin syringe suggest fibrils As with the syringes, the CVs were very high. The TSK Invisible Needle had the highest CV (149.5%), while the BD PrecisionGlide 30G had the lowest CV (35.9%). Nevertheless, no significant difference was seen in the variability of the 10 models evaluated (Fig. 3). Coefficients of variation (CV) (%) of the needle models By studying different syringe and needles samples from the same brand and lot in the current study we identified great variability in the numbers of particles released ranging from 66 to 150% for syringes and from 36 to 150% for needles indicated that the marked variations do not depend on the model or whether it is SO-free the variability in the particles released in the needles from the same lot is of clinical relevance 35%) had the least variability and yet the CV was high in that such variability greatly hinders reliable prediction of particle release under normal clinical conditions and 149.5% (TSK Invisible Needle) cause uncertainty about the outcomes of a procedure such as an IVI a consideration about the release of silicone oil by the needles should be made The source of the silicone oil in the eye from the neddle is more likely due to friction during globe penetration since the siliconization of these devices is made on the outer wall part of this silicone oil can be found on the inner wall of the needles (the part of the needle from which our samples were obtained) and that's the part directly injected into the vitreous which is probably mostly retained externally to the eye studies that evaluate the outer wall of the needles and the release of particles due to friction during globe penetration might help to better clarify the real role of the needles in the release of particles during the IVI The morphologic considerations regarding particles released from needles are similar to particles released from syringes: circular images are consistently seen with SO Other particles such as fibers and plastic also were seen in the needle samples we observed that all studied syringes and needles exhibited great variability in the release of particles with no significant differences among the assessed models ophthalmologists who perform IVIs should be aware of this wide variability in particles from syringes and needles due to the potential clinical implication of particles injected into the vitreous of their patients Better control is needed in the siliconization process and particle loads from these devices which will provide greater safety and increase physicians confidence about their clinical outcomes Four syringes were studied: the SR 1-mL insulin (Saldanha-Rodrigues BD 1-mL Tuberculin Slip Tip (Becton–Dickinson and Co. BD Ultra-Fine 0.3-mL Short Needle with a half-unit-scale (Becton–Dickinson and Co. and HSW Norm-Ject Tuberculin (Henke Sass Wolf the syringes were tested without an attached needle Ten needles were assessed: BD PrecisionGlide 27-(G) (lot #9077702) and 30-(G) (lot #9093839) and BD Eclipse 30-G (lot #8362592) (Becton–Dickinson and Co. and TSK Invisible Needle (lot #204174) and TSK Steriject Control Hub 27-G (lot #204210) and 30-G (lot #204326) (TSK Laboratory and morphology of the microsized particles were characterized using flow imaging microscopy (Flowcam Fluid Imaging Technologies The size range analyzed by the microflow imaging microscopy is from 1 to 100 μm 0.22 µm filtered)—similar to the formulation used with bevacizumab (Avastin USA)—was kindly provided by Vaida Linkuviene (Skaggs School of Pharmacy and Pharmaceutical Sciences A 0.05 mL volume of this protein-free buffer solution was drawn into the syringes This volume was expelled into an Eppendorf tube containing 0.95 mL of the same buffer solution for a volume of 1 mL The solution was mixed gently and analyzed Purified water (0.05 mL) was loaded into the hub of each needle and after a SO-free syringe (HSW Norm-Ject) was attached the water was expelled into an Eppendorf tube containing 0.95 mL of water to make a 1-mL sample This solution also was mixed gently and analyzed All measurements were performed in triplicate for each sample Purified water was used to assure a low background particle count before sample measurement and also between each sample Ten samples of each needle and syringe were assessed The number of particles was analyzed descriptively using summary measures (mean The Feltz and Miller test was used to compare the CVs Statistical analysis were performed using the statistical software R and STATA 12 (SAS Institute No humans or animals were involved in any part of this research The only materials analyzed in all steps were syringes and needles All methods carried out in this research were in accordance with relevant guidelines and regulations applied to all types of research including the ones that do not involve animals or humans subjects The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request Silicone in Pharmaceutical Applications Part 2: Silicone Excipients (Dow Corning Corporation Chan, E., Hubbard, A., Sane, S. & Maa, Y. 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